Inhaled nitric oxide versus aerosolized iloprost for the treatment of pulmonary hypertension with left heart disease.

Objective: To determine the effects of inhaled nitric oxide (NO) and aerosolized iloprost on pulmonary hemodynamics and lung edema formation in a rat model of pulmonary hypertension due to congestive heart failure (CHF). Design: Prospective, randomized, controlled study. Setting: Research laboratory. Subjects: One hundred sixty male Sprague-Dawley rats. Interventions: CHF was induced by supracoronary aortic banding whereas sham-operated rats served as controls. CHF rats or controls inhaled NO, aerosolized iloprost, or 0.9% NaCI for 3 minutes each. Additional CHF groups received intravenous infusions of iloprost, sodium nitroprusside, or 0.9% NaCI. For prolonged drug administration over 150 minutes, NO was inhaled continuously whereas aerosolized iloprost was administered for 3 minutes each at 45-minute intervals. Measurements and Main Results: Dose-response relations in rats with CHF showed a maximal pulmonary-selective reduction in blood pressure at 20 ppm NO and 2.5 μg/mL aerosolized iloprost, with iloprost therapy resulting in a greater decrease in pulmonary arterial pressure (PAP). At these doses, both vasodilators decreased pulmonary vascular resistance and increased venous oxygen saturation (Svo 2 ) in the absence of systemic hemodynamic effects. No pulmonary or systemic effects were detected in rats with CHF inhaling 0.9% NaCI or in control rats inhaling NO or iloprost. Intravenous infusion of iloprost or sodium nitroprusside not only reduced pulmonary but also systemic vascular resistance. During prolonged inhalation, NO caused a stable reduction in PAP, whereas PAP decreased even further during repetitive iloprost inhalations. After 150 minutes, iloprost-treated rats had a higher Svo 2 and lesser edema as compared with animals with CHF inhaling NO or untreated rats with CHF, although differences in wet/dry weight ratio did not reach statistical significance (p < 0.06). Conclusions: Inhaled vasodilators may offer an effective, safe, and pulmonary-selective strategy for the treatment of pulmonary hypertension in left heart disease, and inhaled iloprost may be superior to NO in this condition.